Liver Biopsy Research Articles

Choline-deficient, high-fat diet-induced MASH in Göttingen Minipigs: characterization and effects of a chow reversal period.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is increasing, and translational animal models are needed to develop novel treatments for this disease. The physiology and metabolism of pigs have a relatively high resemblance to humans, and the present study aimed to characterize choline-deficient and high-fat diet (CDAHFD)-fed Göttingen Minipigs as a novel animal model of MASLD/MASH. Göttingen Minipigs were fed CDAHFD for up to 5 mo, and the phenotype was investigated by the analysis of plasma parameters and repeated collection of liver biopsies. Furthermore, changes in hepatic gene expression during the experiment were explored by RNA sequencing. For a subset of the minipigs, the diet was changed from CDAHFD back to chow to investigate whether the liver pathology was reversible. Göttingen Minipigs on CDAHFD gained body weight, and plasma levels of cholesterol, AST, ALT, ALP, and GGT were increased. CDAHFD-fed minipigs developed hepatic steatosis, inflammation, and fibrosis, which in 5 of 16 animals progressed to cirrhosis. During an 11-wk chow reversal period, steatosis regressed, while fibrosis persisted. Regarding inflammation, the findings were less clear, depending on the type of readout. MASH Human Proximity Scoring (combined evaluation of transcriptional, phenotypic, and histopathological parameters) showed that CDAHFD-fed Göttingen Minipigs resemble human MASLD/MASH better than most rodent models. In conclusion, CDAHFD-fed minipigs develop a MASH-like phenotype, which, in several aspects, resembles the changes observed in human patients with MASLD/MASH. Furthermore, repeated collection of liver biopsies allows detailed characterization of histopathological changes over time in individual animals.NEW & NOTEWORTHY The physiology and metabolism of pigs have a relatively high resemblance to humans. This study characterizes a new animal model of MASLD/MASH using CDAHFD-fed Göttingen Minipigs. Göttingen Minipigs fed CDAHFD gained weight and developed hepatic steatosis, inflammation, fibrosis, and cirrhosis. After an 11-wk chow-reversal period, hepatic steatosis and some inflammatory parameters reversed. Combined evaluation of phenotypic, transcriptional, and histological parameters revealed the minipig model showed a higher resemblance to human disease than many rodent models.

Successful transarterial embolization of hemorrhage following percutaneous liver biopsy in hepatic amyloidosis.

Percutaneous liver biopsy is essential for diagnosing hepatic amyloidosis. Post biopsy hemorrhage is unusual but can occur. The potential for bleeding can result from various factors, such as the deposition of amyloid in the hepatic parenchyma or vessel wall, deficiencies in coagulation factors, hyperfibrinolysis, and platelet dysfunction. Transarterial embolization can be a safe and effective method for achieving hemostasis.

Overview of the Etiology, Pathology, and Prognosis of Giant Cell Hepatitis.

Giant cell hepatitis is an important diagnostic consideration in early childhood, especially for patients who present with jaundice. Different diseases may play a role in their etiology. In this study, we presented pediatric patients in our center diagnosed with giant cell hepatitis. Liver biopsies performed in our hospital between January 2010 and December 2023 were retrospectively evaluated, and biopsies with histological giant cell formation were included in the study. Demographic, clinical, and histopathological characteristics of the patients were obtained from the medical records. Our study included 31 cases of giant cell hepatitis. Twenty-four (90.3%) of the patients were male, and the median age was 4 months (range, 1-148 mo). The most common clinical findings were jaundice (93.5%). Among the 31 patients, idiopathic giant cell hepatitis was observed in 13 cases (41.9%), and etiology was elucidated in 18 patients. The most common diagnoses in these patients were progressive familial intrahepatic cholestasis, biliary atresia, and autoimmune hepatitis (22.6%, 19.4%, and 9.7%, respectively). The most common accompanying histopathologic findings were canalicular cholestasis (87.1%), lobular cholestasis (54.8%), and pericellular fibrosis (35.5%). Liver transplant was required in 10 patients (32.3%). Nine patients (29%) died from various reasons. Although follow-up of 13 patients (41.9%) are ongoing, 9 patients (29%) are no longer being followed. Few studies in the pediatric age group on giant cell hepatitis have been conducted in the literature. Similar to our series, etiology could not be specified in most of the patients in these reports. Additional research is needed to improve our understanding of the disease process, uncover any other potential causes, and create specific treatment options.

Indications and Histological Outcomes of Liver Biopsies in Sokoto, Northwestern Nigeria

Background: Various liver disorders require histological assessment for proper diagnosis, staging, treatment, or follow-up. We determine indications and histological outcomes of liver biopsy samples. Materials and Methods: Sixty-two patients were consecutively recruited from four health centers within Sokoto metropolis over a five-year period (March 2019 to February 2023). Fifty one subjects that consented had a liver biopsy done for various indications. The tissues obtained were taken for histopathologic evaluations. Results: In the majority of the subjects, 39 (76.5%) the clinical indications for liver biopsy was Chronic viral Hepatitis infections (CVHI) while 7(13.7%) and 5(9.8) of the subjects had clinical indications of unexplained liver mass and fatty liver disease respectively. In all, fifty one subjects had liver biopsy. Histological outcomes were: Chronic Hepatitis 37 (72.5%), followed by HCC with 6 (11.8%), steatohepatitis 4(7.8%) then one subjects each for steatosis and secondary metastasis to the liver. Among the subjects with histological findings of Chronic Hepatitis majority of them either having mild necroinflammation 13(35.1%) or moderate necroinflammation 14(40.5%). Significant fibrosis was found in over 40% of the patients, with 2(5.6%) had histological conclusion of liver cirrhosis. The degree of inflammation and fibrosis from chronic hepatitis was not statistically significant between genders. Conclusions: Despite advancements made in available facilities in diagnosing liver diseases, tissue still plays a significant role in diagnosis. This is particularly so in regions with hyper- endemicity for CHBVI and low socio-economic standards.

Vibration-controlled transient elastography for significant fibrosis in treatment-naïve chronic hepatitis B patients: A systematic review and meta-analysis.

Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of vibration-controlled transient elastography (VCTE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN). The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of VCTE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of VCTE in the meta-analysis. Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 (95% confidence interval [CI], 0.66-0.86) and 0.72 (95% CI, 0.60-0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72-0.86). The optimal cutoff value of VCTE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50-0.76) and specificity of 0.83 (95% CI, 0.72-0.90). Our study demonstrated that VCTE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Biliary atresia and situs inversus in infant: a rare case report

Background. Biliary atresia is the leading cause of liver transplantation in children. It is associated with other congenital anomalies. The presentation of biliary atresia with situs inversus is a rare case. Case presentation. A 2-month-old female presented with jaundice since 15 days of life, acolic stools, and tea-colored urine. On further evaluation, she was found to have dextrocardia and situs inversus. A liver biopsy was performed and showed hepatic fibrosis due to extrahepatic cholestasis. Abdominal ultrasound and MRCP confirmed a liver in the left hypochondrium and suggested biliary atresia. Conclusion. Although rare, every patient with biliary atresia should be screened for congenital situs inversus, which has a poor prognosis.

Association between triglyceride glucose-body mass index and the staging of non-alcoholic steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease

Objective The objective of this study was to thoroughly investigate the clinical value of triglyceride glucose-body mass index (TyG-BMI) in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). Specifically, we aimed to determine its association with non-alcoholic steatohepatitis (NASH) and the progression of liver fibrosis. Methods The study included 393 patients diagnosed with NAFLD after liver biopsy. The patients were divided into two distinct cohorts: a training cohort (N = 320) and a validation cohort (N = 73). The training cohort was further divided into four groups based on TyG-BMI quartiles. The clinical characteristics of the patients in each group were compared in detail, and the association between TyG-BMI and NASH, NAFLD Activity Score (NAS) ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis was analyzed using multiple models. Additionally, we generated receiver operating characteristic (ROC) curves to evaluate the predictive ability of TyG-BMI for NASH and fibrosis staging in patients with NAFLD. Results Patients with higher TyG-BMI values had a significantly higher prevalence of NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis (all p < .05). TyG-BMI was an independent predictor of these diseases in both unadjusted and adjusted models (all p < .05). ROC curve analysis further revealed the excellent performance of TyG-BMI in predicting NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis. The validation cohort yielded analogous results. Furthermore, we constructed three multivariate models of TyG-BMI in conjunction with elastography metrics, which demonstrated elevated diagnostic AUC values of 0.782, 0.792, 0.794, 0.785, 0.834, and 0.845, respectively. Conclusion This study confirms a significant association between insulin resistance and NAFLD, including at-risk NASH and fibrosis staging, as assessed using the TyG-BMI index. TyG-BMI and its associated multivariate models can be valuable noninvasive indicators for NAFLD diagnosis, risk stratification, and disease course monitoring.

Endoscopic ultrasound-guided tissue acquisition for focal liver lesions can be safely performed in patients with ascites

Background and study aim: In patients with ascites, percutaneous liver biopsy is generally contraindicated. Since endoscopic ultrasound-guided tissue acquisition (EUS-TA) allows tissue sample obtention from the digestive tract lumen, a biopsy without the intervention of ascites may prevent adverse events. This study aimed to evaluate the safety of EUS-TA for focal liver lesions in the presence of ascites. Patients and methods: A retrospective study was conducted using medical records of cases in which EUS-TA was performed on focal liver lesions between 2016 and 2022. Study participants were classified into two groups: those with ascites and those without it, and the outcomes were compared. The primary outcome was adverse events. Results: We included 109 cases of EUS-TA for focal liver lesions. Ascites was present in 20.1% (22/109) of cases and absent in 79.8% (87/109) of cases. There were no significant differences between the two groups in clinical backgrounds and EUS-TA procedure, although fine needle biopsy needles were significantly more frequently used in patients without ascites. In the ascites group, puncture without intervening ascites was successful in 90.9% (20/22) of cases. The incidence of adverse events was 4.5% (1/22) in the ascites group and 1.1% (1/87) in the non-ascites group, showing no significant difference. The two adverse events were mild self-limiting abdominal pain. Conclusions: In focal liver lesions with ascites, EUS-TA allows biopsy without the intervention of ascites in most cases. The incidence of adverse events did not differ significantly between patients with and without ascites.

Ascites of unknown origin in infant: a rare case report

Introduction. Ascites of unknown origin in infants are rare and diagnostically challenging. However, it can be associated with a poor prognosis if it is not treated promptly. Case presentation. A 3-month-old boy infant was admitted to the Dr. Soetomo General Academic Hospital, Surabaya because of a 2-week history of progressive abdominal distension with massive ascites following fever onset. Laboratory parameter measurement revealed increased liver function test, hypoalbuminemia, and prolonged coagulation factor. Hepatitis markers were negative. TORCH serological examination showed non-reactive. Urinalysis, renal function test, and echocardiography were normal. The ascitic fluid analysis showed SAAG &gt;1.1 g/dL. An abdominal ultrasound examination revealed ascites. MRCP showed hepatomegaly and ascites. A liver biopsy showed foci of polymorphonuclear and mononuclear inflammatory cell distribution among hepatocytes with no hepatic fibrosis. He was treated with antibiotics, steroids, diuretics, and albumin transfusion. There were no ascites and laboratory parameters were improved after treatment. Conclusion. Progressive and rapid hepatic inflammatory mechanisms may play a role in the development of ascites. Steroids may be considered in cases of unexplained ascites thought to be related to liver injury to prevent further liver fibrosis.

Spleen shear wave elastography measurements do not correlate with histological grading of liver fibrosis in Fontan physiology: a preliminary investigation.

Elevated spleen stiffness may be seen in patients with portal hypertension due to cirrhosis. In patients with Fontan physiology, elevated liver stiffness has been shown to correlate poorly with liver fibrosis. It is unknown whether spleen stiffness may instead serve as a surrogate marker of liver fibrosis in these patients. To compare spleen stiffness determined by shear wave elastography (SWE) with histological findings of an ultrasound-guided liver biopsy in patients who had undergone Fontan palliation as a potential surrogate for Fontan-associated liver disease. This was an IRB-approved single-center, retrospective study. Patients with Fontan palliation who had undergone both a spleen SWE study and a percutaneous liver biopsy between 2016 and 2020 were included. Biopsy, performed during cardiac catheterization, within 3months of the SWE was required for inclusion. Using Kruskal-Wallis tests, spleen stiffness was compared with three liver biopsy scoring methods: Ishak, METAVIR, and congestive hepatic fibrosis score (CHFS). When available, Pearson's correlation was also used to compare collagen deposition determined using Sirius Red stain (%SR) with SWE values. A P-value < 0.05 was considered statistically significant. Twenty-two patients (15 males) were included in the study, with a median age of 17years (IQR is 14.8-20.5years; age range: 7years to 30.2years). The median spleen stiffness was 2.94m/s (IQR: 2.57-3.61m/s; range: 1.48-4.27m/s). The median Fontan pressure was 11mm Hg (IQR: 10-13.3mm Hg; range: 7-19mm Hg) obtained within a median of 10days (IQR: 1-41days) of SWE. Splenic stiffness did not correlate with the extent of fibrosis determined by histology (all P > 0.05). There was also no statistically significant correlation between the %SR staining and SWE-determined spleen stiffness (Pearson's correlation of 0.165, P = 0.59, n = 13). In this preliminary study, SWE spleen stiffness values did not correlate with biopsy-determined scoring of liver fibrosis in patients with Fontan physiology.

Monocyte subpopulations in children with autoimmune liver disease

BackgroundPatients with autoimmune liver diseases require individualized long-term immunosuppressive therapy, whose discontinuation is possible after complete histological remission and that requires repeated liver biopsy. In view of this, the search for non-invasive markers is essential for patients with autoimmune liver disease. PurposeThe purpose of this research is to assess the possibility of predicting the recurrence of autoimmune liver disease in children. MethodThe biological material used in the study was blood serum from 80 children diagnosed with autoimmune hepatitis and autoimmune sclerosing cholangitis. Patients were divided into four groups according to disease activity and therapeutic approach. ResultsThe percentage of monocyte subpopulations was determined by flow cytometry, and disease activity, inflammation, and fibrosis markers were analyzed to study the relationship and diagnostic value of the parameters studied in detail. The results of the study indicate a significant relationship between disease activity and changes in the distribution of the percentage of monocyte subpopulations in the blood. The percentage of intermediate CD14++/CD16+ monocytes was found to correlate with disease activity, and non-classical CD14lowCD16+ monocytes were found to be of high diagnostic value in the diagnosis of disease relapse. ConclusionsThese findings not only expand the understanding of the pathogenesis of autoimmune liver disease but also point to the prospects of using monocyte subpopulations as potential biomarkers for predicting relapse, contributing to the development of more effective clinical management strategies.

Amyloid precursor protein as a fibrosis marker in infants with biliary atresia.

Biliary atresia (BA) is a rare condition of unknown origin in newborns with jaundice. In BA bile ducts are non-functional, causing neonatal cholestasis and following liver fibrosis and failure. This retrospective study included liver biopsies of 14 infants with BA aged [mean ± SD] 63 ± 23 days. Patients were grouped according to the clinical course (jaundice-free vs recurrent jaundice vs required liver transplantation or liver fibrosis (Ishak fibrosis score)) and followed for 1.61-5.64 years (mean 4.03). Transcriptome profiles were assessed using a panel of 768 fibrosis-specific genes, reanalyzed via qRT-PCR, and confirmed via immunostaining. Plasma from an additional 30 BA infants and 10 age-matched controls were used for amyloid precursor protein (APP) quantification by ELISA. Different clinical outcome groups showed a homogeneous mRNA expression. Altered amyloid-metabolism-related gene expression was found between cases with Ishak fibrosis score greater than 4. Immunostaining confirmed a distinct presence of APP in the livers of all BA subjects. APP plasma levels were higher in BA than in age-matched controls and correlated with the histological fibrosis grade. These results suggest that amyloidosis may contribute to BA and liver fibrosis, indicating that APP could serve as a potential liquid biomarker for these conditions. Biliary atresia patients with higher fibrosis scores according to Ishak have higher hepatic expression of amyloid-related genes while amyloid precursor protein accumulates in the liver and increases in the circulation. After a recent study revealed beta-amyloid deposition as a mechanism potentially involved in biliary atresia, we were able to correlate amyloid-metabolism-related transcript levels as well as amyloid precursor protein tissue and plasma levels with the degree of hepatic fibrosis. These findings suggest that amyloid precursor protein is a fibrosis marker in infants with biliary atresia, reinforcing the role of amyloid metabolism in the pathogenesis of this serious disease.

Application of liver biopsy in etiological diagnosis of unexplained portal hypertension: Porto-sinusoidal vascular disease should not be ignored.

The diagnostic value of liver biopsy has been confirmed in patients with abnormal liver test results; however, little data are available on its application in patients with portal hypertension. This study aimed to investigate the utility of liver biopsy for the etiological diagnosis of unexplained portal hypertension, and explore the clinical and pathological characteristics of each etiology. A retrospective observational analysis was conducted on 1367 patients who underwent liver biopsy at the Second Hospital of Nanjing from 2017 to 2019. Of these, 188 patients with unexplained portal hypertension were enrolled. The clinical and pathological characteristics were collected and reassessed in a multidisciplinary team meeting. Among these patients, 174 (92.6%, 174/188) had a definite etiological diagnosis through liver biopsy. The main etiologies were autoimmune hepatitis in 47 patients (25%, 47/188), autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in 41 patients (21.8%, 41/188), and porto-sinusoidal vascular disease (PSVD) in 40 patients (21.3%, 40/188). Compared to liver cirrhosis, PSVD patients were younger and the liver function damage of which was subtler. The widths of portal vein diameter were widest in PSVD but the liver stiffness measurement were almost normal. Splenomegaly was common in PSVD, but ascites were less frequent than in autoimmune hepatitis (25.0% vs 51.1%, P = .013). Based on the histological patterns, we found that cholestatic liver diseases such as primary biliary cirrhosis, autoimmune hepatitis-primary biliary cirrhosis overlap syndrome, and progressive familial intrahepatic cholestasis could lead to non-cirrhotic portal hypertension, while vascular liver diseases such as PSVD and Budd-Chiari syndrome could also show fibrous proliferation as the disease progresses. Liver biopsy is safe and valuable for etiological diagnosis of unexplained portal hypertension. Cirrhosis is the leading cause of portal hypertension, and porto-sinusoidal vascular diseases should also be considered. Clinical features may be helpful in suggesting the cause; however, pathological examination is still indispensable for disease diagnosis and progression assessment.

Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases.

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis. The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed. Case 1, a Hispanic male from Puerto Rico with hepatomegaly since age 2 months, was eventually diagnosed with PFIC3 following identification of a homozygous splice site variant in ATP binding cassette subfamily B member 4 (ABCB4) (c.2784-12T>C) at age 17 years by whole-exome sequencing (WES). Case 2 was a 37-year-old man with a history of alcoholism, abnormal liver function tests, and ductopenia on biopsy. Molecular testing revealed a pathogenic heterozygous ABCB4 mutation (c.1633C>T) variant leading to a diagnosis of PFIC3. Case 3 was a 2-year-old female initially presenting as a drug-induced liver injury but was diagnosed with PFIC10 following identification of a heterozygous frameshift mutation (p.Asp300Trpfs*19) and a heterozygous missense mutation (c.1357T>C) in myosin VB (MYO5B) by WES. These PFIC cases highlight the heterogenous presentation and diagnostic challenges, and they emphasize the role of next-generation sequencing, particularly the utility of WES.

Transient elastography and diffusion-weighted magnetic resonance imaging for assessment of liver fibrosis in children with chronic hepatitis C.

Chronic hepatitis C (CHC) is a health burden with consequent morbidity and mortality. Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment. Noninvasive alternatives for liver biopsy such as transient elastography (TE) and diffusion-weighted magnetic resonance imaging (DW-MRI) are critical needs. To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC. This prospective cross-sectional study initially recruited 100 children with CHC virus infection. Sixty-four children completed the full set of investigations including liver stiffness measurement (LSM) using TE and measurement of apparent diffusion coefficient (ADC) of the liver and spleen using DW-MRI. Liver biopsies were evaluated for fibrosis using Ishak scoring system. LSM and liver and spleen ADC were compared in different fibrosis stages and correlation analysis was performed with histopathological findings and other laboratory parameters. Most patients had moderate fibrosis (73.5%) while 26.5% had mild fibrosis. None had severe fibrosis or cirrhosis. The majority (68.8%) had mild activity, while only 7.8% had moderate activity. Ishak scores had a significant direct correlation with LSM (P = 0.008) and were negatively correlated with both liver and spleen ADC but with no statistical significance (P = 0.086 and P = 0.145, respectively). Similarly, histopathological activity correlated significantly with LSM (P = 0.002) but not with liver or spleen ADC (P = 0.84 and 0.98 respectively). LSM and liver ADC were able to significantly discriminate F3 from lower fibrosis stages (area under the curve = 0.700 and 0.747, respectively) with a better performance of liver ADC. TE and liver ADC were helpful in predicting significant fibrosis in children with chronic hepatitis C virus infection with a better performance of liver ADC.

Evaluation of the effect of cannabidiol administration with and without nonsteroidal anti-inflammatory drugs in dogs with mobility disorders: a prospective, double-blind, crossover, placebo-controlled study.

With rapidly growing interest in the use of cannabidiol (CBD) in the management of pain and other conditions, more information is needed on the safety and efficacy of this supplement, particularly its co-administration with commonly used pharmaceuticals such as non-steroidal anti-inflammatory drugs (NSAIDs). This study sought to assess the effect of CBD in dogs with mobility impairments, as well as evaluate the clinical tolerance of CBD used together with NSAIDs. Forty-two client-owned dogs with diagnosed mobility impairments were enrolled in this prospective, double-blind, crossover, placebo-controlled study. Baseline data were collected for 10-14 days followed by random allocation to either placebo or CBD oil for 45 days with a 30-day washout period in between. CBD was dosed at 5 mg/kg orally every 12 h with masked placebo administered at equal volume. Outcome measures included objective gait analysis, accelerometry, and clinical metrology instruments. CBD plasma levels and serum biochemistry were also collected along with hepatic ultrasound if warranted. Thirty-eight dogs finished the study with thirty-nine included for at least partial analysis. Compared to baseline, dogs receiving CBD showed evidence of improved outcomes based on blinded veterinary assessments and accelerometer data. Compared to placebo, dogs receiving CBD showed some evidence of improved outcomes on CBPI, CSOM, and blinded veterinary assessments, but not for objective outcome measures. There was evidence of increased ALP when CBD was co-administered with NSAIDs compared to CBD administration alone. Additionally, there was evidence of ALT elevations with CBD and NSAID co-administration, but this elevation did not show evidence of an increase over CBD use alone. These results suggest a potential therapeutic benefit in the administration of CBD for the management of mobility impairments, but greater ALP elevations were seen when administered with NSAIDs. While the sample size of dogs that received further hepatic work-up for liver enzyme elevations is small, chosen diagnostics varied, and liver biopsies were not performed, there did not appear to be clinically apparent liver damage. Further research is needed to better understand the efficacy of CBD in a larger population of dogs and patient tolerance and safety when administered with NSAIDs or other medications long term.

Identifying metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus using clinic-based prediction tools.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a global cause of chronic liver disease. The prevalence of MASLD is high in patients with type 2 diabetes mellitus (T2DM). Various non-invasive tools such as the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), liver ultrasound, and FibroScan can aid in the detection of liver fibrosis in MASLD, while the Hamaguchi ultrasound-based liver grading system has demonstrated high sensitivity and specificity comparable to liver biopsy. We assessed the frequency of MASLD in patients with T2DM using the liver ultrasound Hamaguchi score and the accuracy of NFS and Fib-4 in identifying MASLD. We retrospectively collected data and reviewed the charts of all patients with T2DM who underwent liver ultrasound and laboratory tests during the past 5 years. A total of 6,214 medical records were screened, and only 153 patients (68.6% women; mean age, 59 ± 12.2 years) fulfilled the selection criteria. MASLD was diagnosed using the Hamaguchi grading criteria in 45.1% of patients. A high/intermediate NFS had a higher sensitivity (79.7%) for diagnosing MASLD with a specificity of 10.7%, while a high/intermediate Fib-4 score showed only 30.4% sensitivity but a higher specificity of 54.8%. Our study indicates that MASLD is frequent in patients with T2DM, and clinical prediction tools such as NFS and Fib-4 can be applied in clinic/primary care settings with variable results.

Obesity increases the risk of hepatic fibrosis in young adults with type 2 diabetes mellitus: the need to screen.

The objective of this study was to determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in young compared with older adults. Individuals (n = 1420) with (63%) and without type 2 diabetes mellitus (T2D; 37%) who attended internal medicine clinics and did not have a known history of MASLD underwent laboratory evaluation and transient elastography to assess for hepatic steatosis and fibrosis. Magnetic resonance elastography and liver biopsy were recommended when indicated. A total of 243 participants were ages <45 years, and 1177 were ages ≥45 years. Obesity, T2D, and metabolic syndrome were highly prevalent in young adults. Frequencies of steatosis and fibrosis were high in young adults (50.2% and 7.5% vs. older adults 52.7% and 9.9%, respectively) and were significantly higher in those with both obesity and T2D (71.1% and 15.7%, respectively; p < 0.01). In young adults, T2D and obesity were the strongest risk factors for hepatic fibrosis (odds ratios 4.33 [95% CI: 1.37-13.68] and 1.16 [95% CI: 1.07-1.25], respectively; p < 0.05). There is a high prevalence of clinically significant hepatic fibrosis in young adults with cardiometabolic risk factors. Up to one in seven young adults with obesity and T2D had clinically significant hepatic fibrosis on elastography. This highlights the need to screen young adults with cardiometabolic risk factors for MASLD for early detection and intervention.

Primary Biliary Cholangitis in Men: A Case Report

Primary biliary cholangitis (PBC) is a rare chronic autoimmune liver disease, especially in men, that causes progressive inflammation and destruction of the intrahepatic bile ducts. This leads to hepatic fibrosis that can progress to cirrhosis. PBC diagnosis is suggested by cholestatic jaundice in the absence of abnormalities in intrahepatic and extrahepatic bile ducts, with alkaline phosphatases (ALP) &gt; 1.5 times the upper limit of normal and gamma-glutamyl transferase (GGT) &gt; 3 times the upper limit of normal, with or without elevated bilirubin levels. Confirmation is made through immunological tests, and liver biopsy (PBH) is necessary if tests are negative. The disease is often diagnosed at an advanced stage. Poor prognostic factors include early diagnosis, male gender, severe symptoms, and biological abnormalities such as elevated bilirubin levels. Specific autoantibodies, such as anti-gp210 and anti-sp100, also predict unfavorable disease progression. The first-line treatment is ursodeoxycholic acid (UDCA), which helps slow disease progression and improve symptoms. If UDCA is ineffective, other options include obeticholic acid (OCA) or fibrates like bezafibrate, often used in combination with UDCA. Liver transplantation is the only curative treatment for severe cases. Research is ongoing for new treatments, including PPAR agonists and bile acid transporter inhibitors.

Magnetic resonance spectroscopy as a diagnostic model for assessment of liver steatosis in metabolic dysfunction-associated steatotic liver disease in non-diabetic patients

BackgroundMetabolic dysfunction-associated steatotic liver (MASLD) disease is the commonest hepatic cause of liver fibrosis and cirrhosis after the introduction of the direct acting antivirals and eradication of hepatitis C. MASLD is usually associated with metabolic syndrome and elevated inflammatory markers. Magnetic resonance spectroscopy (MRS) offers a non-invasive diagnostic, alternative to liver biopsy. This is a case–control diagnostic-accuracy study conducted on 40 patients in the Hepato-gastroenterology Unit in the Internal Medicine Department, Ain Shams University Hospitals, to study the role of MRI spectroscopy as a new diagnostic model for assessment of liver steatosis in non-diabetic MASLD patients compared to the standard ultrasound and clinical criteria. MASLD was diagnosed by a combination of a validated ultrasound hepatic steatosis score grading system and hepatic steatosis index using clinical and laboratory parameters. MRS was performed in all patients and fat peak, water peak, and fat fraction % were measured, and diagnostic accuracy of different MRS is compared to the US scoring and different laboratory and clinical parameters. To our knowledge this is the first study conducted on MRS in our region and Egypt.ResultsThis study revealed no statistically significant difference between the two groups regarding HbA1C, creatinine, while there was highly statistically significant difference regarding fasting blood sugar, 2 h post-prandial glucose level, urine albumin, and low-density lipoprotein levels. Hepatic steatosis score grading by abdominal ultrasound on the 20 controls showed no fatty changes with grade 0 (50%), and on the 20 MASLD patients showed that 2 cases were grade 1 steatosis (5%), 9 cases were grade 2 steatosis (22.5%), and 9 cases were grade 3 steatosis (22.5%). The diagnostic accuracy of predicting hepatic steatosis using different MRS parameters: fat peak, water peak, and fat fraction had area under the curve of 99.9%, 88.6%, and 100%, respectively. The sensitivity and specificity of fat fraction in detecting hepatic steatosis were 100%. The sensitivity and specificity of the fat peak in detecting hepatic steatosis were 100% and 95%, respectively. Moreover, the sensitivity and specificity of the water peak in detecting the hepatic steatosis were 88.6% and 85%, respectively. There is a statistically significant correlation between the three MRS parameters and the abdominal ultrasound hepatic steatosis score grades.ConclusionMRS parameters: fat fraction, fat peak, and water peak, have high diagnostic accuracy for predicting the liver steatosis. Moreover, MRS has the added advantage of being a non-invasive and a tool with low radiation risk. MRS also shows the metabolic changes in the liver and could be an eligible outcome in therapeutic clinical trials.